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M Buchler

Publications and source records attributed to M Buchler.

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p53 mutations are common in pancreatic cancer and are absent in chronic pancreatitis.

Pancreatic expression of the p53 tumor suppressor gene was studied in pancreatic adenocarcinomas and chronic pancreatitis. By immunohistochemistry, 16 of 34 (47%) cancers and none of the 24 chronic pancreatitis samples revealed nuclear staining. Sequence analysis indicated that 8 of 24 (33%) cancers were mutated for the p53 gene. Point substitutions occurred at codons 35, 105, 133, 213, 213, 258, and 299. A three base-pair in-frame insertion was identified between codons 261 and 262. None of 8 chronic pancreatitis samples exhibited p53 gene mutations. These data support a role for p53 gene alterations in human pancreatic cancer, and suggest that loss of its regulatory functions may constitute one of the differences between pancreatic cancer and chronic pancreatitis.

Adenocarcinoma↗

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Analysis of nerves in chronic pancreatitis.

We sought to identify characteristics of pancreatic nerves that were altered in chronic pancreatitis. Pancreatic tissue removed from patients with chronic pancreatitis was analyzed for the number and size of nerves, their association with inflammatory infiltrates, and their fine structure. The mean diameter of nerves in these patients was significantly greater than in controls, whereas the mean area of tissue served per nerve was significantly less than in controls. Foci of inflammatory cells, prominent in some specimens, sometimes were associated with nerves and ganglia, but inflammatory foci and neural elements also existed separately. Invasion of nerve tissue by inflammatory cells was observed but was not massive. Ultrastructural changes were detected in nerves. Individual nerve fibers showed evidence of damage, and there was evidence of edema in the nerve bundle. The perineurial sheath was altered so that it no longer provided a barrier between the surrounding connective tissue and the internal neural components. The results of this study indicate that nerves are preferentially retained while parenchyma degenerates and is replaced by fibrosis during chronic pancreatitis, but that they are retained in an altered condition. Increased mean diameters of nerves in chronic pancreatitis argues against pain being caused by constriction due to fibrosis. It is likely that both sensory and motor nerve fibers are affected by this alteration.

Adult↗

Renal artery aneurysm secondary to Candida albicans in four kidney allograft recipients.

INTRODUCTION: Infection is a frequent cause of morbidity and mortality in solid organ transplant recipients. It may occur at different periods after transplantation. We report four cases of mycotic aneurysms due to Candida albicans (CA) in renal transplant recipients occurring early after kidney transplantation. CASE REPORTS: Four patients (three men, one woman) aged from 24 to 55 years who underwent cadaveric renal transplantation from three different donors developed a mycotic aneurysm at 9 to 90 days after transplantation. In all cases aneurysms were located at the anastomosis between the renal graft artery and the iliac axis. The clinical presentations were fever in three cases, including endocarditis in one patient or deterioration of graft function in two cases and hemorrhagic shock secondary to a ruptured renal artery in the fourth case, which led to death. The arterial aneurysm was discovered at autopsy. The diagnosis of a mycotic aneurysm was based on morphological investigations: echotomography, spiral computed tomography, and arteriography. In all cases bacteriological studies (blood culture, culture of the aneurysmal wall and content) isolated CA. In three patients CA was isolated from the preservation solution; it was of the same phenotype as the one isolated from the aneurysm in one recipient. Antifungal therapy was started in patients who lived, but all kidney transplants had to be removed. Anatomical results of arterial reconstructions were satisfactory in all cases and remained so during the follow-up. CONCLUSION: The insidious presentation and clinical course of mycotic aneurysms due to CA require a high degree of suspicion to make the correct diagnosis.

Adult↗

p53 expression in human pancreatic cancer correlates with enhanced biological aggressiveness.

Immunohistochemical analysis of the p53 tumor suppressor gene was performed in 69 human pancreatic ductal adenocarcinomas, using a highly specific anti-p53 antibody. Nuclear immunoreactivity was found in 40 tumors, yielding an overall frequency of 58%. Immunoblotting confirmed that nuclear immunoreactivity was associated with increased p53 protein levels. p53 mRNA levels were increased in 9 of 9 tested cancers, without evidence for gene amplification. Analysis of the immunostaining data by chi-square and log-rank indicated that the presence of nuclear immunoreactivity correlated with a more advanced clinical stage, and a statistically significant decrease in the post-operative survival period. In 12 cancers, metastatic tissue samples were also available for p53 analysis. Nuclear p53 immunostaining in the primary tumors was not always associated with p53 immunoreactivity in the metastatic samples, and metastases occurred in the absence of nuclear p53 immunoreactivity in the primary lesion. These findings suggest that increased p53 protein levels in human pancreatic cancer may be due not only to p53 mutations which attenuate the degradation of the protein but also to an increase in p53 mRNA levels leading to increased p53 synthesis, and that p53 nuclear immunoreactivity in these cancers implies enhanced tumor aggressiveness but is not essential for the development of metastases.

Antibody Specificity↗

Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness.

Immunohistochemical analysis for the epidermal growth factor receptor (EGFR), EGF and transforming growth factor-alpha (TGF-alpha) was performed in 87 human pancreatic carcinomas. Expression frequencies for EGFR, EGF, and TGF-alpha were 43%, 46% and 54%, respectively. Coexpression of the receptor and at least one of its ligands occurred in 38% of the tumors, and correlated with large tumor size, advanced clinical staging, and decreased survival period. In situ hybridization revealed that the respective mRNAs were also overexpressed in the carcinomas. These findings suggest that coexpression of EGFR and its ligands may contribute to the aggressiveness of human pancreatic cancer.

Adult↗